TY - JOUR
T1 - Migration against the direction of flow is LFA-1 dependent in human hematopoietic stem and progenitor cells
JF - Journal of Cell Science
JO - J. Cell Sci.
M3 - 10.1242/jcs.205575
AU - Buffone, Alexander
AU - Anderson, Nicholas R.
AU - Hammer, Daniel A.
Y1 - 2017/01/01
UR - http://jcs.biologists.org/content/early/2017/11/24/jcs.205575.abstract
N2 - The recruitment of immune cells during inflammation is regulated by a multi-step cascade of cell rolling, activation, adhesion, and transmigration through the endothelial barrier. Similarly, Hematopoietic Stem and Progenitor Cells (HSPCs) use this pathway to migrate and home to the bone marrow. After selectin-mediated braking, HSPCs migrate along the vascular endothelium on adhesion ligands including ICAM-1, VCAM-1 or MAdCAM-1. Here we report that both the KG1a stem cell line and primary bone marrow CD34+ HSPCs can migrate against the direction of fluid flow on surfaces coated with cell adhesion molecules (CAMs), a behavior thus far only reported in T lymphocytes. We demonstrate that KG1a cells and primary HSPCs migrate upstream on ICAM-1, downstream on VCAM-1, and both upstream and downstream on MAdCAM-1. Also, we demonstrate that KG1a cells and HSPCs display upstream migration both on surfaces with multiple CAMs, as well as on HUVEC monolayers. By blocking with monoclonal antibodies, we show that Lymphocyte Function-associated Antigen-1 (LFA-1) is the key receptor responsible for upstream migration along the endothelium during the trafficking of HSPCs to the bone marrow.
ER -